EzCatDB: M00225
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DB codeM00225
CATH domainDomain 12.30.40.10 : Urease, subunit C; domain 1
Domain 23.20.20.140 : TIM BarrelCatalytic domain
Domain 32.10.150.10 : Urease, subunit B
Domain 43.30.280.10 : Urease; subunit A
E.C.3.5.1.5

CATH domainRelated DB codes (homologues)
2.10.150.10 : Urease, subunit BM00030,M00226
2.30.40.10 : Urease, subunit C; domain 1D00673,D00675,D00801,D00873,M00030,M00226
3.20.20.140 : TIM BarrelS00231,S00232,M00186,D00673,D00675,D00801,D00873,M00030,M00226
3.30.280.10 : Urease; subunit AM00030,M00226

Enzyme Name
UniProtKBKEGG

P69996D3UJ80P14916D3UJ81
Protein nameUrease subunit beta
Urease subunit alpha
Urease
Urea amidohydrolase
SynonymsEC 3.5.1.5
Urea amidohydrolase subunit beta
NoneEC 3.5.1.5
Urea amidohydrolase subunit alpha
None
RefSeqNP_206872.1 (Protein)
NC_000915.1 (DNA/RNA sequence)
YP_006933994.1 (Protein)
NC_018939.1 (DNA/RNA sequence)
YP_003517278.1 (Protein)
NC_013949.1 (DNA/RNA sequence)
NP_206873.1 (Protein)
NC_000915.1 (DNA/RNA sequence)
YP_006933995.1 (Protein)
NC_018939.1 (DNA/RNA sequence)
YP_003517279.1 (Protein)
NC_013949.1 (DNA/RNA sequence)
MEROPSM38.982 (Metallo)
M38.982 (Metallo)


PfamPF01979 (Amidohydro_1)
PF00449 (Urease_alpha)
[Graphical view]
PF01979 (Amidohydro_1)
PF00449 (Urease_alpha)
[Graphical view]
PF00699 (Urease_beta)
PF00547 (Urease_gamma)
[Graphical view]
PF00699 (Urease_beta)
PF00547 (Urease_gamma)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00220Urea cycle and metabolism of amino groups
MAP00230Purine metabolism
MAP00791Atrazine degradation

UniProtKB:Accession NumberP69996D3UJ80P14916D3UJ81
Entry nameURE2_HELPYD3UJ80_HELM1URE23_HELPYD3UJ81_HELM1
ActivityUrea + H(2)O = CO(2) + 2 NH(3).Urea + H(2)O = CO(2) + 2 NH(3).Urea + H(2)O = CO(2) + 2 NH(3).Urea + H(2)O = CO(2) + 2 NH(3).
SubunitHeterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits. Four heterohexamers assemble to form a 16 nm dodecameric complex.Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits (By similarity).Heterohexamer of 3 UreA (alpha) and 3 UreB (beta) subunits. Four heterohexamers assemble to form a 16 nm dodecameric complex.
Subcellular locationCytoplasm. Note=Also associates with the outer membrane upon autolysis of neighboring bacteria.Cytoplasm (By similarity).Cytoplasm. Note=Also associates with the outer membrane upon autolysis of neighboring bacteria.
CofactorBinds 2 nickel ions per subunit.Binds 2 nickel ions per subunit (By similarity).


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00291C00086C00001C00011C00014I00127C01563
CompoundNickelUreaH2OCO2NH3DiaminohydroxymethanolateCarbamate
Typeheavy metalamide group,amine groupH2Oothersamine group,organic ion

ChEBI28112
16199
48376
15377
16526
16134


PubChem935
1176
962
22247451
280
222


               
1e9yB01UnboundUnbound UnboundUnboundUnboundUnbound
1e9zB01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaC01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaF01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaI01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaL01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaO01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaR01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkC01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkF01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkI01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkL01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkO01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkR01UnboundUnbound UnboundUnboundUnboundUnbound
1e9yB02Bound:2x_NIUnbound UnboundUnboundUnboundIntermediate-analogue:HAE
1e9zB02Bound:2x_NIUnbound UnboundUnboundUnboundUnbound
3qgaC02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgaF02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgaI02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgaL02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgaO02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgaR02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgkC02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgkF02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgkI02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgkL02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgkO02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
3qgkR02Analogue:2x_FEUnbound UnboundUnboundUnboundUnbound
1e9yA01UnboundUnbound UnboundUnboundUnboundUnbound
1e9zA01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaA02UnboundUnbound UnboundUnboundUnboundUnbound
3qgaD02UnboundUnbound UnboundUnboundUnboundUnbound
3qgaG02UnboundUnbound UnboundUnboundUnboundUnbound
3qgaJ02UnboundUnbound UnboundUnboundUnboundUnbound
3qgaM02UnboundUnbound UnboundUnboundUnboundUnbound
3qgaP02UnboundUnbound UnboundUnboundUnboundUnbound
3qgkA02UnboundUnbound UnboundUnboundUnboundUnbound
3qgkD02UnboundUnbound UnboundUnboundUnboundUnbound
3qgkG02UnboundUnbound UnboundUnboundUnboundUnbound
3qgkJ02UnboundUnbound UnboundUnboundUnboundUnbound
3qgkM02UnboundUnbound UnboundUnboundUnboundUnbound
3qgkP02UnboundUnbound UnboundUnboundUnboundUnbound
1e9yA02UnboundUnbound UnboundUnboundUnboundUnbound
1e9zA02UnboundUnbound UnboundUnboundUnboundUnbound
3qgaA01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaD01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaG01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaJ01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaM01UnboundUnbound UnboundUnboundUnboundUnbound
3qgaP01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkA01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkD01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkG01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkJ01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkM01UnboundUnbound UnboundUnboundUnboundUnbound
3qgkP01UnboundUnbound UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P18314, P41020, P69996 & literature [17], [22], [31]
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
1e9yB01 
 
 
 
1e9zB01 
 
 
 
3qgaC01 
 
 
 
3qgaF01 
 
 
 
3qgaI01 
 
 
 
3qgaL01 
 
 
 
3qgaO01 
 
 
 
3qgaR01 
 
 
 
3qgkC01 
 
 
 
3qgkF01 
 
 
 
3qgkI01 
 
 
 
3qgkL01 
 
 
 
3qgkO01 
 
 
 
3qgkR01 
 
 
 
1e9yB02HIS  221;ASP  223;HIS  322;ARG  338
KCX  219(Nickel-1 & -2);HIS  248;HIS  274(Nickel-1);HIS  136;HIS  138;ASP  362(Nickel-2)
KCX  219(Carbamylated LYS)
 
1e9zB02HIS  221;ASP  223;HIS  322;ARG  338
KCX  219(Nickel-1 & -2);HIS  248;HIS  274(Nickel-1);HIS  136;HIS  138;ASP  362(Nickel-2)
KCX  219(Carbamylated LYS)
 
3qgaC02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgaF02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgaI02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgaL02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgaO02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgaR02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgkC02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgkF02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgkI02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgkL02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgkO02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
3qgkR02HIS  220;ASP  222;HIS  321;ARG  337
KCX  218(Nickel-1 & -2);HIS  247;HIS  273(Nickel-1);HIS  135;HIS  137;ASP  361(Nickel-2)
KCX  218(Carbamylated LYS)
invisible 329-332
1e9yA01 
 
 
 
1e9zA01 
 
 
 
3qgaA02 
 
 
 
3qgaD02 
 
 
 
3qgaG02 
 
 
 
3qgaJ02 
 
 
 
3qgaM02 
 
 
 
3qgaP02 
 
 
 
3qgkA02 
 
 
 
3qgkD02 
 
 
 
3qgkG02 
 
 
 
3qgkJ02 
 
 
 
3qgkM02 
 
 
 
3qgkP02 
 
 
 
1e9yA02 
 
 
 
1e9zA02 
 
 
 
3qgaA01 
 
 
 
3qgaD01 
 
 
 
3qgaG01 
 
 
 
3qgaJ01 
 
 
 
3qgaM01 
 
 
 
3qgaP01 
 
 
 
3qgkA01 
 
 
 
3qgkD01 
 
 
 
3qgkG01 
 
 
 
3qgkJ01 
 
 
 
3qgkM01 
 
 
 
3qgkP01 
 
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]figure, p.996
[12]Figure 2, Figure 6, p.333-337
[17]Figure 8, p.211-213
[19]Figure 7, p.5394-5395
[20]FIGURE 1, FIGURE 8, p.8583-8584
[22]Figure 2, Figure 3, Figure 4, p.796
[23]

[24]Fig.6, p.787
[31]Figure 3, Figure 7, Figure 8, Figure 10, p.15335-15337
[34]Figure 13, p.6943
[35]Figure 4, Figure 11, p.11842
[36]Figure 4, Figure 5, Figure 6, Figure 13, Figure 16, Figure 18
[37]Figure 1, Figure 2, Figure 3
[40]Scheme 2, p.521

references
[1]
PubMed ID1400317
JournalJ Biol Chem
Year1992
Volume267
Pages20024-7
AuthorsMartin PR, Hausinger RP
TitleSite-directed mutagenesis of the active site cysteine in Klebsiella aerogenes urease.
[2]
PubMed ID1404395
JournalJ Mol Biol
Year1992
Volume227
Pages934-7
AuthorsJabri E, Lee MH, Hausinger RP, Karplus PA
TitlePreliminary crystallographic studies of urease from jack bean and from Klebsiella aerogenes.
[3]
PubMed ID8318888
JournalProtein Sci
Year1993
Volume2
Pages1034-41
AuthorsPark IS, Hausinger RP
TitleSite-directed mutagenesis of Klebsiella aerogenes urease: identification of histidine residues that appear to function in nickel ligation, substrate binding, and catalysis.
[4]
PubMed ID7565414
JournalMicrobiol Rev
Year1995
Volume59
Pages451-80
AuthorsMobley HL, Island MD, Hausinger RP
TitleMolecular biology of microbial ureases.
[5]
PubMed ID8535259
JournalProtein Sci
Year1995
Volume4
Pages2234-6
AuthorsMoncrief MB, Hom LG, Jabri E, Karplus PA, Hausinger RP
TitleUrease activity in the crystalline state.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID95273988
PubMed ID7754395
JournalScience
Year1995
Volume268
Pages998-1004
AuthorsJabri E, Carr MB, Hausinger RP, Karplus PA
TitleThe crystal structure of urease from Klebsiella aerogenes.
Related PDB1kau,2kau,3kau
Related UniProtKBP18314,P18315,P18316
[7]
PubMed ID7754394
JournalScience
Year1995
Volume268
Pages996-7
AuthorsLippard SJ
TitleAt last--the crystal structure of urease.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID96346054
PubMed ID8718850
JournalBiochemistry
Year1996
Volume35
Pages10616-26
AuthorsJabri E, Karplus PA
TitleStructures of the Klebsiella aerogenes urease apoenzyme and two active-site mutants.
Related PDB1kra,1krb,1krc
Related UniProtKBP18314,P18315,P18316
[9]
CommentsX-ray crystallography
PubMed ID8702515
JournalJ Biol Chem
Year1996
Volume271
Pages18632-7
AuthorsPark IS, Michel LO, Pearson MA, Jabri E, Karplus PA, Wang S, Dong J, Scott RA, Koehler BP, Johnson MK, Hausinger RP
TitleCharacterization of the mononickel metallocenter in H134A mutant urease.
Related PDB1fwi
[10]
CommentsX-ray crystallography
PubMed ID9201965
JournalBiochemistry
Year1997
Volume36
Pages8164-72
AuthorsPearson MA, Michel LO, Hausinger RP, Karplus PA
TitleStructures of Cys319 variants and acetohydroxamate-inhibited Klebsiella aerogenes urease.
Related PDB1fwa,1fwb,1fwc,1fwd,1fwe,1fwf,1fwg,1fwh,1fwj
[11]
PubMed ID9144792
JournalProteins
Year1997
Volume28
Pages72-82
AuthorsHolm L, Sander C
TitleAn evolutionary treasure: unification of a broad set of amidohydrolases related to urease.
[12]
JournalAcc Chem Res
Year1997
Volume30
Pages330?7
AuthorsKarplus PA, Pearson MA, Hausinger RP
Title70 Years of Crystalline Urease:? What Have We Learned?
[13]
CommentsX-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
PubMed ID9761912
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages409-12
AuthorsBenini S, Ciurli S, Rypniewski WR, Wilson KS, Mangani S
TitleCrystallization and preliminary high-resolution X-ray diffraction analysis of native and beta-mercaptoethanol-inhibited urease from Bacillus pasteurii.
Related UniProtKBP41020,P41021,P41022
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID98226663
PubMed ID9558361
JournalBiochemistry
Year1998
Volume37
Pages6214-20
AuthorsPearson MA, Schaller RA, Michel LO, Karplus PA, Hausinger RP
TitleChemical rescue of Klebsiella aerogenes urease variants lacking the carbamylated-lysine nickel ligand.
Related PDB1a5k,1a5l,1a5m,1a5n,1a5o
Related UniProtKBP18314,P18315,P18316
[15]
CommentsX-ray crystallography
JournalJ Biol Inorg Chem
Year1998
Volume3
Pages268-73
AuthorsBenini S, Rypniewski WR, Wilson KS, Ciurli S, Mangani S
TitleThe complex of Bacillus pasteurii urease with beta-mercaptoethanol from X-ray data at 1.65-angstrom resolution.
Related PDB1ubp
[16]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
PubMed ID10555581
JournalJ Biol Inorg Chem
Year1999
Volume4
Pages468-77
AuthorsYamaguchi K, Cosper NJ, Stalhandske C, Scott RA, Pearson MA, Karplus PA, Hausinger RP
TitleCharacterization of metal-substituted Klebsiella aerogenes urease.
Related PDB1ef2
Related UniProtKBP18314,P18315,P18316
[17]
CommentsX-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID99148127
PubMed ID10368287
JournalStructure Fold Des
Year1999
Volume7
Pages205-16
AuthorsBenini S, Rypniewski WR, Wilson KS, Miletti S, Ciurli S, Mangani S
TitleA new proposal for urease mechanism based on the crystal structures of the native and inhibited enzyme from Bacillus pasteurii: why urea hydrolysis costs two nickels.
Related PDB2ubp,3ubp
Related UniProtKBP41020,P41021,P41022
[18]
PubMed ID11996109
JournalActa Biochim Pol
Year2000
Volume47
Pages1189-95
AuthorsSirko A, Brodzik R
TitlePlant ureases: roles and regulation.
[19]
PubMed ID10820010
JournalBiochemistry
Year2000
Volume39
Pages5389-96
AuthorsTodd MJ, Hausinger RP
TitleFluoride inhibition of Klebsiella aerogenes urease: mechanistic implications of a pseudo-uncompetitive, slow-binding inhibitor.
[20]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), AND MUTAGENESIS OF HIS-219; ASP-221; HIS-320 AND ARG-336.
PubMed ID10913264
JournalBiochemistry
Year2000
Volume39
Pages8575-84
AuthorsPearson MA, Park IS, Schaller RA, Michel LO, Karplus PA, Hausinger RP
TitleKinetic and structural characterization of urease active site variants.
Related PDB1ejr,1ejs,1ejt,1eju,1ejv
Related UniProtKBP18314,P18315,P18316
[21]
CommentsX-ray crystallography
PubMed ID10766443
JournalJ Biol Inorg Chem
Year2000
Volume5
Pages110-8
AuthorsBenini S, Rypniewski WR, Wilson KS, Miletti S, Ciurli S, Mangani S
TitleThe complex of Bacillus pasteurii urease with acetohydroxamate anion from X-ray data at 1.55 A resolution.
Related PDB4ubp
[22]
PubMed ID10798524
JournalJ Biomol Struct Dyn
Year2000
Volume17
Pages787-97
AuthorsZimmer M
TitleMolecular mechanics evaluation of the proposed mechanisms for the degradation of urea by urease.
[23]
JournalJ Am Chem Soc
Year2000
Volume122
Pages9172-77
AuthorsBarrios AM, Lippard SJ
TitleInteraction of Urea with a Hydroxide-Bridged Dinuclear Nickel Center:? An Alternative Model for the Mechanism of Urease.
[24]
CommentsX-ray crystallography
PubMed ID11713685
JournalJ Biol Inorg Chem
Year2001
Volume6
Pages778-90
AuthorsBenini S, Rypniewski WR, Wilson KS, Ciurli S, Mangani S
TitleStructure-based rationalization of urease inhibition by phosphate: novel insights into the enzyme mechanism.
Related PDB1ie7
[25]
PubMed ID11315566
JournalJ Biol Inorg Chem
Year2001
Volume6
Pages300-14
AuthorsMusiani F, Arnofi E, Casadio R, Ciurli S
TitleStructure-based computational study of the catalytic and inhibition mechanisms of urease.
[26]
PubMed ID11373609
JournalNat Struct Biol
Year2001
Volume8
Pages480-2
AuthorsDunn BE, Grutter MG
TitleHelicobacter pylori springs another surprise.
[27]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), AND SUBUNIT STRUCTURE.
PubMed ID11373617
JournalNat Struct Biol
Year2001
Volume8
Pages505-9
AuthorsHa NC, Oh ST, Sung JY, Cha KA, Lee MH, Oh BH
TitleSupramolecular assembly and acid resistance of Helicobacter pylori urease.
Related PDB1e9y,1e9z
Related UniProtKBP14916,P69996
[28]
PubMed ID11300826
JournalInorg Chem
Year2001
Volume40
Pages1250-5
AuthorsBarrios AM, Lippard SJ
TitleDecomposition of alkyl-substituted urea molecules at a hydroxide-bridged dinickel center.
[29]
PubMed ID11807281
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages374-6
AuthorsSheridan L, Wilmot CM, Cromie KD, van der Logt P, Phillips SE
TitleCrystallization and preliminary X-ray structure determination of jack bean urease with a bound antibody fragment.
[30]
PubMed ID12121941
JournalAntimicrob Agents Chemother
Year2002
Volume46
Pages2613-8
AuthorsMishra H, Parrill AL, Williamson JS
TitleThree-dimensional quantitative structure-activity relationship and comparative molecular field analysis of dipeptide hydroxamic acid Helicobacter pylori urease inhibitors.
[31]
PubMed ID14664576
JournalJ Am Chem Soc
Year2003
Volume125
Pages15324-37
AuthorsSuarez D, Diaz N, Merz KM Jr
TitleUreases: quantum chemical calculations on cluster models.
[32]
PubMed ID12913138
JournalPlant Physiol
Year2003
Volume132
Pages1801-10
AuthorsGoldraij A, Beamer LJ, Polacco JC
TitleInterallelic complementation at the ubiquitous urease coding locus of soybean.
[33]
CommentsX-ray crystallography
PubMed ID15038715
JournalJ Am Chem Soc
Year2004
Volume126
Pages3714-5
AuthorsBenini S, Rypniewski WR, Wilson KS, Mangani S, Ciurli S
TitleMolecular details of urease inhibition by boric acid: insights into the catalytic mechanism.
Related PDB1s3t
[34]
PubMed ID15174863
JournalJ Am Chem Soc
Year2004
Volume126
Pages6932-44
AuthorsEstiu G, Merz KM Jr
TitleThe hydrolysis of urea and the proficiency of urease.
[35]
PubMed ID15382918
JournalJ Am Chem Soc
Year2004
Volume126
Pages11832-42
AuthorsEstiu G, Merz KM Jr
TitleEnzymatic catalysis of urea decomposition: elimination or hydrolysis?
[36]
PubMed ID16584179
JournalBiochemistry
Year2006
Volume45
Pages4429-43
AuthorsEstiu G, Merz KM Jr
TitleCatalyzed decomposition of urea. Molecular dynamics simulations of the binding of urea to urease.
[37]
PubMed ID17676790
JournalJ Phys Chem B
Year2007
Volume111
Pages10263-74
AuthorsEstiu G, Merz KM Jr
TitleCompetitive hydrolytic and elimination mechanisms in the urease catalyzed decomposition of urea.
[38]
PubMed ID20471401
JournalJ Mol Biol
Year2010
Volume400
Pages274-83
AuthorsBalasubramanian A, Ponnuraj K
TitleCrystal structure of the first plant urease from jack bean: 83 years of journey from its first crystal to molecular structure.
Related PDB3la4
[39]
PubMed ID21788478
JournalProc Natl Acad Sci U S A
Year2011
Volume108
Pages13095-9
AuthorsCarter EL, Tronrud DE, Taber SR, Karplus PA, Hausinger RP
TitleIron-containing urease in a pathogenic bacterium.
Related PDB3qga,3qgk
[40]
PubMed ID21542631
JournalAcc Chem Res
Year2011
Volume44
Pages520-30
AuthorsZambelli B, Musiani F, Benini S, Ciurli S
TitleChemistry of Ni2+ in urease: sensing, trafficking, and catalysis.

comments
There are several types of urease enzymes based on the composition of subunits. This enzyme is composed of two subunits, one of which has a catalytic domain.
According to the literature, at least three catalytic mechanisms have been reported. Two mechanisms for hydrolysis, which proceeds through a tetrahedral intermediate (diaminohydroxymethanolate) that gives finally carbamate and ammonia (see [12], [17] and [20]). One mechanism for elimination, which proceeds through an intermediate, cyanic acid (see [23] and [28]).
(i) Hydrolysis by a reverse protonation mechanism: Carbonyl oxygen of urea is bound to Nickel-1, whereas a hydrolytic water is bound to Nickel-2. The hydrolytic water makes a nucleophilic attack on the carbonyl carbon of urea, forming a tetrahedral intermediate (diaminohydroxymethanolate). His322 (PDB;1e9y) acts as a general acid to protonate a leaving amino group, although the residue has a low pKa. Thus, carbamate and an ammonia can be produced. (see [12], [14], [19] and [20])
(ii) Hydrolysis by nucleophilic attack of a bridging hydroxide: Carbonyl oxygen of urea is bound to Nickel-1, whereas an amine group is bound to Nickel-2. The bridging hydroxide between the two nickel ions acts as a nucleophile, which attacks on the carbonyl carbon, forming a tetrahedral intermediate. The Asp residue, which is bound to Nickel-2, transfers proton from the hydroxyl group of the intermediate to the leaving amine group. His322 may stabilize the intermediate, rather than acting as a general acid. (see [17], [24], [33] and [40])
(iii) Elimination through cyanic acid (see [23], [28], [35], [36] and [37])
Alghough these reported mechanisms lead to a debate, the hydrolysis mechanism by bridging hydroxide seems to be the most reasonable, from structural viewpoints.

createdupdated
2005-10-182012-03-23


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